Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast.

Abstract:

:Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork stalled at the lesion site, the replication checkpoint presumably coordinates the action of lesion bypass processes with the replisome. However, it has remained unclear as to which of the lesion bypass processes-translesion synthesis (TLS) and/or template switching-depend on the activation of the replication checkpoint. Here we determine if the Mec1 kinase and the subunits of the checkpoint clamp and the clamp loader are required for TLS. We show that proficient TLS can occur in the absence of these checkpoint proteins in nucleotide excision repair (NER)-proficient cells; however, in the absence of NER, checkpoint protein-mediated Rev1 phosphorylation contributes to increasing the proficiency of DNA polymerase zeta-dependent TLS.

journal_name

Genes Dev

journal_title

Genes & development

authors

Pagès V,Santa Maria SR,Prakash L,Prakash S

doi

10.1101/gad.1793409

subject

Has Abstract

pub_date

2009-06-15 00:00:00

pages

1438-49

issue

12

eissn

0890-9369

issn

1549-5477

pii

23/12/1438

journal_volume

23

pub_type

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